Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome

NCT ID: NCT04614506

Last Updated: 2022-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

6 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-02

Study Completion Date

2022-12-31

Brief Summary

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Dravet syndrome (DS) is an epileptic encephalopathy caused by pathogenic variants in the SCN1A gene resulting in medically refractory epilepsy and psychomotor delays.

As a pilot study assessing for feasibility, the investigators aim to test whether alterations in cortical excitatory:inhibitory ratio can be reliably recorded. The investigators will utilize transcranial magnetic stimulation (TMS) metrics of cortical excitatory and inhibitory tone as an initial step towards translating findings from rodent genetic models of DS into disease-specific biomarkers and offer future measures of therapeutic target engagement in this patient population.

Participants will complete two visits, each consisting of a TMS session and an EEG session. Visits will be scheduled 4-8 weeks apart.

Detailed Description

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This is a single site study to be conducted at Boston Children's Hospital (BCH) investigating the neurophysiological biomarkers of epilepsy and developmental disability in children and young adults with Dravet Syndrome.

Mechanistically, the features of the DS phenotype are attributable to a loss of cortical inhibition. TMS is a non-invasive form of focal cortical stimulation in which an external powerful magnet induces an electrical field intracranially over the stimulated region that is used to interrogate or modulate states of cortical excitation or inhibition.

Accordingly, the investigators propose to test whether metrics of cortical excitability and inhibition can be obtained by transcranial magnetic stimulation (TMS) and EEG in patients with DS.

Conditions

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Dravet Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Subject with DS

Participants will complete two visits spaced out by 4 - 8 weeks to undergo neurophysiological assessments (Electroencephalogram \[EEG\], and Transcranial magnetic stimulation \[TMS\]).

Transcranial Magnetic Stimulation (TMS)

Intervention Type DEVICE

Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.

Electroencephalogram (EEG)

Intervention Type DEVICE

These will be an ambulatory EEG recordings that span 24 hours and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.

Interventions

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Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.

Intervention Type DEVICE

Electroencephalogram (EEG)

These will be an ambulatory EEG recordings that span 24 hours and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.

Intervention Type DEVICE

Other Intervention Names

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Nexstim Navigated Brain Stimulation (NBS) System 4 Natus

Eligibility Criteria

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Inclusion Criteria

* Age: 6 months - 30 years
* Ability to obtain informed consent with the participant or legally authorized representative
* DS confirmed by pathogenic variant in SCN1A gene
* Medical history consistent with clinical phenotype of DS

Exclusion Criteria

* Comorbid conditions such as a second genetic diagnosis which may confound interpretation.
* Current or planned participation in a clinical drug or device trial.
* Previous participation in a gene therapy or gene editing trial
* Allergy to adhesives used for surface EMG electrodes
* Contraindications to TMS (e.g. implanted devices for which there is no TMS safety data)
Minimum Eligible Age

6 Months

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Encoded Therapeutics

INDUSTRY

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Alexander Rotenberg

Associate, Department of Neurology; Director, Neuromodulation Program; Associate Professor of Neurology, Harvard Medical School

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexander Rotenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Paul MacMullin

Role: CONTACT

617-355-4875

Melissa Tsuboyama, MD

Role: CONTACT

Facility Contacts

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Paul MacMullin

Role: primary

Other Identifiers

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IRB-P00034206

Identifier Type: -

Identifier Source: org_study_id

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